Synthesis, central nervous system activity and teratogenicity of a homothalidomide.
The optical isomers of alpha-phthalimidoadipinimide (1) were synthesized by a route based on D(+)- and L(-)-amino-epsilon-caprolactam (5) as synthon. The isomers of 1 were obtained in high yields by treating D(+)- and L(-)-amino-epsilon-caprolactam (5) with N-carboethoxyphthalimide (4), followed by oxidation with benzeneseleninic anhydride (7). The teratogenic potency of both isomers of 1 was studied by the HET-(Hen's Egg Test); 1 caused distinctly lower teratogenic effects in contrast to thalidomide (2). D(-)-1 and L(+)-1 showed sedative effects with a lower activity than 2. Both are more stable in alkaline solution at the same time with a smaller tendency for racemization.
Eger
K
K
Pharmazeutisches Institut, Universität Tübingen, Fed. Rep. of Germany.
Jalalian
M
M
Verspohl
E J
EJ
Lüpke
N P
NP
D000818:Animals; D002642:Chick Embryo; D005260:Female; D006863:Hydrogen-Ion Concentration; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013723:Teratogens; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity*
D006993:Hypnotics and Sedatives; D013723:Teratogens; D013792:Thalidomide